The present invention relates to ophthalmic compositions comprising a xcex2-blocker.
Ophthalmic compositions comprising xcex2-blockers are used in the treatment of ocular hypertension and of glaucoma. As examples, there may be mentioned collyria based on carteolol, timolol, befunolol, metipranolol, levobunolol, pindolol or betaxolol. These solutions have a relatively short duration of action, such that the administration of these collyria should be repeated during the day.
Cohen et al. (Journal of Control Release, 44, 201, 1997) have moreover proposed aqueous solutions of pilocarpine containing a sodium alginate with a high guluronic acid content, which form a gel when the solution is applied to the eye (apparently because of the action of the calcium ions present in the lachrymal fluid) and make it possible to obtain a prolonged duration of action.
The inventors have however observed that if this system is applied to xcex2-blockers, that is to say if a xcex2-blocker is added to a sodium alginate solution, no prolonged effect is obtained after administration of the solution.
The inventors have on the other hand discovered that if a xcex2-blocker is added to an aqueous composition containing alginic acid and the pH is increased by addition of an alkaline base, a solution is obtained which makes it possible to obtain a prolonged effect after administration and which thereby allows a single daily administration.
The subject of the present invention is thus an ophthalmic composition comprising a xcex2-blocker in solution, this composition being obtained by dissolving the xcex2-blocker in water in the presence of alginic acid and adding an alkaline base, in order to obtain a solution having a pH of 6 to 8.
The subject of the present invention is also a method of preparing an ophthalmic composition, consisting in dissolving a xcex2-blocker in water in the presence of alginic acid and in adding an alkaline base in order to bring its pH to a value of 6 to 8.
The alginic acid is preferably an alginic acid having a guluronic acid content of at least 40% and, preferably, of at least 65%, for example an alginic acid having a guluronic acid content of 65 to 75%.
The xcex2-blockers present in the composition may be chosen in particular from carteolol, timolol, befunolol, metipranolol, levobunolol, pindolol or betaxolol.
The xcex2-blockers are added in general in the form of salts with pharmaceutically acceptable acids.
They are generally present at concentrations of 0.01 to 5% and preferably of 0.1 to 2% (expressed in the form of a base) of the weight of the final composition.
The alginic acid is used at concentrations of 0.01 to 5% and, preferably, between 0.1 and 2% of the weight of the final composition.
The alginic acid/xcex2-blocker (expressed in the form of a base) weight ratio is in general from 0.1 to 20 and preferably from 0.2 to 10.
The alkaline base is an alkali metal hydroxide or a basic salt of an alkali metal and is preferably sodium hydroxide.
The composition may in addition contain a buffer mixture such as a phosphate buffer, an isotonizing agent such as sodium chloride, stabilizers such as an antioxidant and/or a chelating agent (for example EDTA), as well as a preservative such as benzalkonium chloride.
Results of trials demonstrating the effects obtained with the compositions according to the invention will be given below.